Metam-sodium

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary source.

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

Repeated dose inhalation Toxicity study of Metam-sodium in Rats .

Author:

European Commission

Year:

2000

Bibliographic source:

European Commission, European Chemicals Bureau, 2000

Reference 2

Reference Type:

secondary source

Title:

Repeated dose inhalation Toxicity study of Metam-sodium in Rats

Author:

US EPA

Year:

1994

Bibliographic source:

United states environment protection agency, 1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

To evaluate the toxicity of Metam Sodium in Sprague–Dawley male and female rats for subacute study.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Metam-sodium

EC Number:

205-293-0

EC Name:

Metam-sodium

Cas Number:

137-42-8

Molecular formula:

C2H5NS2.Na

IUPAC Name:

sodium (methylcarbamothioyl)sulfanide

Test material form:

solid: crystalline

Details on test material:

- Name of test material : Metam-sodium
- Molecular formula : C2H4NNaS2
- Molecular weight : 129.1826 g/mol
- Smiles notation : C(=S)(NC)[S-].[Na+]
- InChl : 1S/C2H5NS2.Na/c1-3-2(4)5;/h1H3,(H2,3,4,5);/q;+1/p-1
- Substance type: Organic
- Physical state: Solid

Specific details on test material used for the study:

- Name of test material : Metam-sodium
- Molecular formula : C2H4NNaS2
- Molecular weight : 129.1826 g/mol
- Smiles notation : C(=S)(NC)[S-].[Na+]
- InChl : 1S/C2H5NS2.Na/c1-3-2(4)5;/h1H3,(H2,3,4,5);/q;+1/p-1
- Substance type: Organic
- Physical state: Solid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

not specified

Details on inhalation exposure:

Not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

Not specified

Duration of treatment / exposure:

3 weeks

Frequency of treatment:

daily – 4 hours per day

Doses / concentrations

Remarks:

0.51, 1.54 and 4.53 mg/l

No. of animals per sex per dose:

0.51, 1.54 and 4.53 mg/l

Control animals:

yes, concurrent vehicle

Details on study design:

Not specified

Examinations

Observations and examinations performed and frequency:

Observations and examinations performed & frequency
CAGE SIDE OBSERVATIONS: Not specified.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

BODY WEIGHT: Not specified .

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified - Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: At the end of
the study ophthalmology l was performed.



HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the end of
the study hematology was performed.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At the end of the study clinical chemistry was performed.



URINALYSIS: Yes
- Time schedule for collection of urine: At the end of the study urinalysis was performed.



NEUROBEHAVIOURAL EXAMINATION: Not specified

Sacrifice and pathology:

Sacrifice and pathology
GROSS PATHOLOGY: Yes, At the end of the study gross–pathological examinations were performed.

HISTOPATHOLOGY: Yes , At the end of the study
histological examinations were performed.

Statistics:

Not specified

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

During 21 days of treatment with the test substance no influence on the animals was seen at the low dose level (0.51 mg/l)

Mortality:

mortality observed, treatment-related

Description (incidence):

The treated animals being exposed to the highest dose (4.53 mg/l) 1 female and 10 males died during the study. No mortality observed in control.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

At the medium dosage (1.54 g/l) body weight gain of both sexes in treated group was markedly inhibited compare to control .
At the high dosage (4.53 mg/l) body weight gain was markedly diminished) in treated group compare to control.

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

At the medium dosage (1.54 g/l) hemoglobin content in male and female and the number of leukocytes were
increased (only females) in treated group was markedly inhibited compare to control.

At the high dosage (4.53 mg/l) hemoglobin content,
erythrocyte–and platelet count in blood were increased.
Leucocytes and reticulocytes were slightly reduced in treated group compare to control.

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

At the medium dosage (1.54 g/l) Organ weights (except adrenals of the males) were reduced) in treated group was markedly inhibited compare to control.

At the high dosage (4.53 mg/l) the weighed internal organs showed markedly reduced absolute values, whereas relative lung weight was increased

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

At the medium dosage (1.54 g/l) histopathological examinations showed pulmonary lesions (alveolar emphysema) in treated group was markedly inhibited compare to control.

At the high dosage (4.53 mg/l) microscopic examination showed multiple pulmonary lesions, thymic atrophy, hyperplasia and depletion, inhibited spermiogenesis, atrophic prostate, tracheitis, changes in the urinary bladder and inflammatory, partly purulent, degenerations in the nasal cavity, maxillary sinus and meatus which might be due to the treatment.

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

0.51 other: mg/l

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant effct were observed at this dose

Remarks on result:

other: No toxic effct were observed

Target system / organ toxicity

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

NOAEL was considered to be 0.51 mg/l for Metam Sodium in Sprague–Dawley male and female rats for subacute study by inhalation route.

Executive summary:

Repeated dose inhalation study ofMetam Sodium was assessed for its possible toxic nature.For this purpose subacute study was conducted on Sprague–Dawley male and female rats by using test substance at the concentration of0.51, 1.54 and 4.53 mg/l. The test substance was exposed daily – 4 hours per day for 3 weeks. The animals were observed for mortality, clinical chemistry, body weight, hematology, organ weight histopathology and gross pathology. Significant effect were observed at the medium dosage (1.54 g/l) and high dosage (4.53 mg/l) . During 21 days of treatment with the test substance no influence on the animals was seen at the low dose level (0.51 mg/l). Therefore NOAEL was considered to be 0.51 mg/l forMetam Sodium in Sprague–Dawley male and female rats for subacute study by inhalation route.